title: Dihydroartemisinin induces autophagy by suppressing NF-κB activation.
abstract: Nuclear factor-kappa B (NF-κB) and autophagy are two major regulators involved in both tumor initiation and progression. However, the association between these two signaling pathways still remains obscure. In this work, we demonstrate that dihydroartemisinin (DHA) stimulates the induction of autophagy in several cancer cell lines through repression of NF-κB activity. We also show that inhibiting NF-κB results in an accumulation of reactive oxygen species (ROS), which participate in the stimulation of autophagy. These findings present a pathway by which DHA promotes autophagy in cancer cells and provide evidence for the DHA-induced sensitization effect of some chemotherapeutics.
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Sang-Sang
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Xiao-E
authors.initials: XE
authors.lastname: Lou
authors.affiliation: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China. Electronic address: zhouhj_zhouhj@yahoo.com.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D016328:NF-kappa B; C039060:artenimol
keywords: 4-Hydroxy-TEMPO; AO; AVOs; Autophagy; CQ; Chloroquine; DHA; DHE; Dihydroartemisinin; FHC; IκB; MnSOD; NF-κB; ROS; TNF-α; Tempo; Translocation; acidic vesicular organelles; acridine orange; dihydroartemisinin; dihydroethidium; ferritin heavy chain; inhibitory subunit of NF-κB; manganese superoxide dismutase; nuclear factor-kappa B; reactive oxygen species; tumor necrosis factor-α